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INTRODUCTION: Despite a two‐fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome‐wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within‐dataset results were meta‐analyzed, followed by functional genomics analyses. RESULTS: A novel AD‐risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, p = 3.68×10−9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10−7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD‐associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. Highlights: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies.The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa.Single variant meta‐analysis identified a novel genome‐wide significant AD‐risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome‐wide significance at p < 9×10−7.Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus.These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry‐informed genetic screening tools and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Nickel(II) complexes of tridentate NNO donor aroylhydrazones, viz., di‐2‐pyridyl ketone‐4‐methoxybenzhydrazone monohydrate (DKMBH·H2O) and 2‐acetylpyrazine‐4‐methoxybenzhydrazone monohydrate (APMBH·H2O), were synthesized and characterized using various methods, including spectral techniques (Fourier transform infrared [FT‐IR], UV–vis) and analytical methods (elemental and X‐ray diffraction [XRD] analysis). Single‐crystal XRD was used to elucidate the crystal structures of nickel(II) complexes 1 and 2. The XRD analysis revealed that the respective ligands coordinated to the Ni(II) center through the deprotonated iminolate form in complex 1 and the neutral amido form in complex 2, resulting in distorted octahedral geometries. The ground state electronic configurations of the complexes were studied using the B3LYP/UB3LYP levels of DFT. Using absorption spectral titration methods, the interactions of complexes with CT‐DNA and bovine serum albumin (BSA) protein were examined. The observed data demonstrate that the complexes adopt an intercalative binding mode to bind to CT‐DNA and BSA protein. Additionally, the antioxidant activity of the nickel(II) complexes and their ligands was determined using 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH). Complex 2 demonstrated the highest radical scavenging activity of the compounds studied (IC50 = 3.81 mM). Furthermore, molecular docking studies were performed to understand how the complexes can interact with the SARS‐CoV‐2 main protease. The results revealed that complex 2 had the highest docking score (−8.18 kcal/mol) when compared with the other complexes under study. Aside from their biological properties, the nickel complexes heterogenized on functionalized SBA‐15 showed promising catalytic activity, achieving 98% yield in the reduction of nitrobenzene, forming exclusively aniline as the end product. [ABSTRACT FROM AUTHOR]

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings. Aims: The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres. Methods: Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed. Results: Forty‐eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46–65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre‐ and post‐TIPS were 10 (IQR: 4.5–16) and 2 (IQR: 0–4) respectively (P < 0.001). There were no procedure‐related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre‐TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post‐TIPS (P < 0.001). Conclusions: TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Implications for nursing policy Internationally qualified nurses are highly sought after as a labour source due to continued shortages in the nursing profession in most developed countries. However, the lack of clear policies and procedures for nurses in the host country to use specialty nursing skills can result in the underutilisation of their expertise.To review the registration processes of internationally qualified nurses in 20 developed countries, with a focus on the transferability of specialised skills gained overseas.A multicentre policy review design was used, using the STROBE reporting guidelines. The study sourced policy information from nurse registration bodies in developed countries and reviewed and removed redundant policies.Out of 34 policies initially identified, 26 were used to show the registration process of nurses after immigration to developed countries. Only four of the 20 countries reviewed indicated the option of specialised nurse registration on their website for internationally qualified nurses, with a university qualification required before years of experience. All other countries indicated the general registration pathway only.More attention is needed to address the lack of well‐defined policies that guide the utilisation of internationally qualified nurses' specialised skills. Transparent procedures are essential to fully benefit from their expertise in the host country's health workforce. [ABSTRACT FROM AUTHOR]

This article discusses the challenges faced by artisan fishers in southwestern India due to uncertain and extreme weather conditions, particularly during the monsoon season. Regular weather forecasts often do not provide enough information for fishers to make safe decisions about going out to fish. The article explores the use of a localized marine weather information service, using the Weather Research Forecasting (WRF) model, to improve the safety of artisan fishing. The study validates the effectiveness of the WRF model in predicting near-surface wind for small boat fishers in south India, based on local demand. [Extracted from the article]

This study proposes an 'implicit measure' of disagreement to investigate presence of any latent discord in the policy briefings of central banks across nations. We analyse Monetary policy statements of the Bank of Japan (Japan), Banco Central do Brasil (Brazil) and Central Bank of the Republic of Turkey (Türkiye) on both specific as well as overall economic outlook by using novel text mining tools. Subsequently, we explore the relationship of the proposed measure of implicit disagreement with the accuracy of growth and inflation forecasts. Our findings confirm that disagreement/discord among policymakers over varied economic aspects provides signals to forecasters and helps in aligning their forecasts better. The results of this study indicate that disagreement too can be considered as a plausible criterion that can explain the forecaster's belief thereby playing a positive role in 'forecaster learning'. [ABSTRACT FROM AUTHOR]

In this study, a Cu‐supported amine‐functionalized Fe3O4 nanocatalyst (Fe3O4‐NH2‐Cu) has been synthesized for A3 (amine, aldehyde, and alkyne) coupling reactions. The synthesized nanocatalyst was characterized by PXRD, FT‐IR, FESEM‐EDX, XPS, and VSM analysis. The catalytic action of the synthesized Fe3O4‐NH2‐Cu nanocatalyst was evaluated for A3 coupling reactions, with an excellent product yield of 97% in propargylamine synthesis and 98% in indolizines synthesis, respectively. The substrate scope of the catalyst was validated for various amines, substituted aryl aldehydes, and phenyl acetylene. The uniqueness of the synthesized nanocatalyst is effective performance of the catalyst under solvent‐free conditions and less reaction time for the aforementioned application. With the aid of an external magnet, the catalyst can be easily recovered from the reaction mixture and reused at least for five times without significant loss in catalytic activity, and its structural stability was confirmed by XRD, FT‐IR, and FESEM‐EDX analysis of the recovered catalyst. Overall, it is a green approach to synthesize simple Fe3O4‐NH2‐Cu catalytic system with magnetic recoverability, reusability, and recyclability for A3 coupling reactions under solvent‐free conditions with broad substrate scope. The proposed plausible mechanism is supported by DFT studies. [ABSTRACT FROM AUTHOR]

Background: Recruitment of internationally qualified nurses as a labour source is a long‐standing human resource strategy being implemented to address the current and increasing global nursing shortage. Internationally qualified nurses transitioning into the health workforce of developed countries following immigration often possess specialty skills. A lack of a clear pathway of specialty skill utilisation makes recognising and using these specialty skills complex for many nurses. The ability for nurses to transition between countries and maintain specialty practice demands immediate attention in the current atmosphere of the global pandemic and the predictions to recruit more specialist nurses from overseas. Aim: To identify and synthesise strategies taken by various developed countries in transitioning specialist internationally qualified nurses into practice. Methods: An integrative review was conducted to identify common themes, patterns, and best practices in order to inform policy development and improve the successful integration of internationally qualified nurses into the healthcare systems of developed countries. The study employed the Whittemore and Knafl five‐stage integrative review approach. To conduct a comprehensive search, four electronic databases, namely Medline, CINAHL Complete, ProQuest Health, and EMBASE, were systematically searched in October 2021. The search was updated in March 2022 to ensure the inclusion of the most recent literature. Additionally, Google Scholar was utilised to avoid overlooking any important articles. Prior to the full‐text review, three reviewers independently evaluated titles and abstracts. The included papers' quality was determined using the JBI critical appraisal tools. Results: This study included 10 papers, comprising three studies and seven reports. However, none of these documents provided information on how internationally qualified nurses could transfer their specialty skills acquired overseas to developed countries after immigrating. The guidelines and policies reviewed only offered generic advice on becoming a specialist nurse. Although some countries mentioned that post‐graduate qualifications were not mandatory for nurse specialists, the majority of documents in this review emphasised the need for a national framework of education at level eight or higher (equivalent to a post‐graduate level) to attain the status of a nurse specialist. Moreover, the included documents did not provide clear information on whether an international specialisation degree would be recognised during the registration process. As a result, confusion persists regarding the requirement of post‐graduate qualifications for nurses aiming to specialise and the recognition of international specialisation degrees during the registration process. Discussion: The lack of consistency in defining nurse specialty and the skill transferability among institutions and state borders were evident in this review. According to all the 10 documents analysed, developed countries appear to have minimum policies on the transfer of internationally qualified nurse's specialty skills. Recommendations for policymakers, employers, and aspirant migrants have been proposed. Limited research has been done on how developed countries used their internationally qualified nurses' overseas‐acquired specialist skills after immigration, indicating a lack of a distinct specialist skill transition pathway. Conclusions: This review presents data to support the need for greater research in this area to better utilise the abilities that internationally qualified nurses bring from their home country and put them to constructive use in the host country, especially in the context of a global pandemic. [ABSTRACT FROM AUTHOR]

The necessity for the development and enhancement of teacher commitment to satisfying students' learning needs in response to the COVID crisis is increasingly highlighted. It is not known, however, how to increase commitment in schoolteachers to boost online teaching in light of the fact that they, too, are struggling to cope with the rapid, unexpected change. A total of 601 teachers from primary and secondary schools across China participated in this study, with an average teaching experience of 15.9 years. Structural equation modelling was used to verify the significance of contextual, cognitive, affective and behavioural factors in boosting teachers' commitment to online teaching. The findings demonstrated that teacher agency played a complete mediating role in the predicting power of other factors to teacher commitment. Therefore, it was recommended that attention be paid to the practice and opportunities for teacher agentic actions, which necessitates real encounters with online teaching, allowing teachers to act meaningfully and initiate a new set of teaching strategies. Practitioner notesWhat is already known about this topic The large‐scale transition to emergency online teaching serves as the catalyst for creating a blended or hybrid model of education provision in the long term.How hard teachers work to perform at their best and overcome obstacles to support students' learning needs in new environment relies on the intensity of teacher commitment to change.Online and blended learning requires teachers to not only be prepared for a diverse learning environment but also to build and rebuild their own identity as future teachers.What this paper adds This study adds to our knowledge of how traditional F2F classroom teachers reinvented their roles and responsibilities in response to the pandemic‐driven challenges based on real‐world experiences.As a result of the COVID‐19 lockdown school closures, schoolteachers' commitment to enhancing online teaching efforts has increased.The study highlights the complete mediating role of teacher agency in the predicting power of cognitive and affective factors to teacher commitment.Implications for practice and/or policy To learn more about how to be a good online teacher, future teachers need greater deliberate effort in diverse online teaching activities.Future teachers should be equipped with not only new technological and remote instructional strategies and skills, but also with confidence in, value for, and actual experiences with online teaching in a technology‐rich environment.For teachers to obtain hands‐on experience in integrating technology with distance teaching pedagogy at a time of rapid change, schools should have some days online and offer blended learning opportunities wherever possible. [ABSTRACT FROM AUTHOR]

Introduction: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. Methods: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). Results: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross‐state variation. Discussion: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. Highlights: The estimated dementia prevalence for adults ages 60+ in India is 7.4%.About 8.8 million Indians older than 60 years live with dementia.Dementia is more prevalent among females than males and in rural than urban areas.Significant cross‐state variation exists in dementia prevalence. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to study the efficacy of UV‐C light emitting diode (LED) system operating at 263 nm for the inactivation of Listeria monocytogenes and Escherichia coli O157:H7. UV‐C irradiation was applied to stirred 5 ml samples, using a collimated beam LED system operating at a 263 nm wavelength. UV irradiation doses ranging from 0 to 160 mJ/cm2 were also delivered to apple juice (AJ) and polyphenols and vitamins were profiled. Liquid chromatography–mass spectrometry (LC–MS/MS) analysis was conducted to assess the stability of polyphenols or vitamins in UV‐C exposed AJ. The polyphenol and vitamin results demonstrated that UV‐C irradiation in AJs at relevant commercial UV doses induced significant reductions in the concentrations of selected polyphenols and vitamins, p <.05. Ascorbic acid was reduced to 32%, at 160 mJ/cm2 whereas 17% reduction was observed at 40 mJ/cm2. Riboflavin was observed to be relatively stable. Epicatechin and chlorogenic were significantly reduced at high exposure doses. In contrast, minor changes were observed at 40 mJ/cm2. Results show that UV‐C irradiation effectively inactivated pathogenic microbes in AJ. Inactivation levels of all organisms were proportional to UV‐C dose. The log reduction kinetics of microorganisms followed log‐linear and with higher R2 (>0.95). The decimal reduction dose (D10) values of 4.16 and 3.84 mJ/cm2 were obtained from the inactivation of E. coli and L. monocytogenes in AJ. The results from this study imply that adequate log reduction of pathogens is achievable in AJ and suggests significant potential for UV‐C treatment of other opaque liquid foods. [ABSTRACT FROM AUTHOR]

Deoxyribose nucleic acid (DNA) is found to be the most efficient pharmacological target of many synthetic molecules which are deemed as potential drugs with clinical applications. DNA binding agents are known to regulate several cell functions (gene expression and replication) by adopting various protocols which include the annihilation of the cell membrane, interruption in protein synthesis, and irreversible binding to cell receptors. Recently, several studies have explored fundamental aspects of drug‐DNA interactions, providing new insights into the driving forces that render the formation of the drug‐DNA complex. In order to study and understand these biologically important reaction mechanisms, several screening tools have been devised and the specificity of drug molecules binding to DNA were studied in detail. This review will discuss the utilization of various analytical tools which include UV‐vis spectroscopy, fluorescence spectroscopy, circular dichroism, viscosity measurement, Raman spectroscopy, cyclic voltammetry, and DNA fragmentation assay used for studying drug binding mode and the mechanism involved. [ABSTRACT FROM AUTHOR]

Non‐invasive approaches using remotely controllable nanomaterials have demonstrated their potential ability to enhance treatment efficacy in regenerative medicine and tissue repair. Although magnetic nanoparticles (MNPs) have been used for multiple healthcare applications where their remote control properties can show significant advances, enhanced surface functional groups, and electrical properties would expand their capabilities. To address this, in this study, MNPs incorporated Graphene Oxide (GO) based nanocomposites (GOMNPs) are developed and functionalized with TREK1 and Piezo1 antibodies to specifically target the respective mechanosensitive ion channels. Magnetic ion channel activation (MICA) technology is used to remotely activate MG63 osteoblast‐like cells tagged with these functionalized GOMNPs. Remote activation of mechanotransduction pathways shows significant upregulation in osteogenic gene expression as well as enhanced alkaline phosphate activity and calcium mineralization with enhanced bone formation. The development of a GOMNP composite has extensive applicability for future clinical translation. [ABSTRACT FROM AUTHOR]

Herein, we report two novel multidentate luminogen proligands bis(3,5‐diiodosalicylidene) carbohydrazone (H4L1) and bis(3,5‐diiodosalicylidene) thiocarbohydrazone (H4L2), which are suitable candidates for biomedical applications. Though the thiocarbohydrazone H4L2 shows aggregation caused quenching (ACQ), the carbohydrazone H4L1 exhibits stronger fluorescence due to aggregation induced emission enhancement (AIEE). Molecular docking studies of H4L1 and H4L2 along with four similar (thio)carbohydrazones with the active sites of SARS‐CoV‐2 main protease 3CLpro reveals that the thiocarbohydrazones, in general, are showing better propensity compared to their oxygen analogues. Both the thiocarbohydrazones and the carbohydrazones, however, exhibit better binding potential at the active sites than that of some of the repurposed drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, darunavir and remdesivir. Also, the carbohydrazone H4L1 can be a better bioprobe compared to H4L2 as the former is found to have better binding potential with SARS‐CoV‐2 spike glycoprotein along with AIEE feature. [ABSTRACT FROM AUTHOR]

Head posture influences the collapsibility of the passive upper airway during anaesthesia. However, little is known about the impact of head posture during sleep. The objective of this study was to develop and validate an instrument to measure head posture during supine sleep and to apply this instrument to investigate the influence of head posture on obstructive sleep apnea (OSA) severity. A customized instrument to quantify head flexion and rotation during supine sleep was developed and validated in a benchtop experiment. Twenty‐eight participants with suspected OSA were successfully studied using diagnostic polysomnography with the addition of the customized instrument. Head posture in supine sleep was discretized into four categories by two variables: head flexed or not (flexion >15°); and head rotated or not (rotation >45°). Sleep time in each posture and the posture‐specific apnea–hypopnea index (AHI) were quantified. Linear mixed‐effect modelling was applied to determine the influence of flexion and rotation on supine OSA severity. Twenty‐four participants had ≥15 min of supine sleep in at least one head‐posture category. Only one participant had ≥15 min of supine sleep time with the head extended. Head flexion was associated with a 12.9 events/h increase in the AHI (95% CI: 3.7–22.1, p =.007). Head rotation was associated with an 11.0 events/h decrease in the AHI (95% CI: 0.3–21.6, p =.04). Despite substantial interparticipant variability, head flexion worsened OSA severity, and head rotation improved OSA severity. Interventions to promote rotation and restrict flexion may have therapeutic benefit in selected patients. [ABSTRACT FROM AUTHOR]

Background: Although African Americans are twice as likely to develop Alzheimer's Disease (AD), individuals with African ancestry are under‐represented in genetic research of the disease. In the largest AD genome‐wide association studies to date for African‐Americans (Reitz et al. JAMA 2013; Kunkle at al. JAMA Neurol 2021) we previously identified several novel susceptibility loci in addition to APOE, including ABCA7, API5, RBFOX1, and IGF1R. Method: We performed a genome‐wide association meta‐analysis of 2,844 AD cases and 6,251 cognitively healthy controls of African ancestry (AA) assembled across 17 different cohorts. Single‐variant association analysis was conducted adjusting for age, sex, principal components, and subsequently APOE, applying logistic regression for case‐control and general estimating equations for family‐based datasets. Within‐study results were meta‐analyzed using METAL, and followed by gene‐based, pathway, scRNA‐seq, and colocalization analyses. Result: Single variant meta‐analysis identified a novel genome‐wide significant AD risk locus in the MPDZ gene on chromosome 9p23 (rs141610415, MAF =.002, P = 3.68×10−9). MPDZ (MUPP1) is a vital component of the NMDAR signaling complex in excitatory synapses of hippocampal neurons critical for learning and memory. Two additional novel common loci and 9 novel rare loci approached genome‐wide significance at P<9×10−7. Genes at these loci are acting in biologically plausible pathways: signal transduction (PLEKHG1), synaptic transmission (CNTNAP4), synaptic connectivity (SDK1), neural development/function (SRGAP3, KIDINS220, UNC5C, TSSC1, TANC2), and neuronal differentiation (ASCL1). Single‐cell RNA‐sequence analysis shows that all genes are expressed in the brain, and that expression of the orthologs of SRGAP3, TANC2, and MMP16 is upregulated with amyloid toxicity in zebrafish. Pathway analyses support the notion that immune response, transcription/DNA repair, lipid processing, and intracellular trafficking are major AD‐associated pathways in African Americans. Except for SIPA1L2 and ACER3, all previously reported loci, including ABCA7, API5, RBFOX1 and IGF1R, remain genome‐wide or close to genome‐wide significant. Conclusion: We identified several novel loci for AD in individuals with African ancestry with the strongest association observed for MPDZ involved in hippocampal synaptic signaling. Identification of a significant number of loci at suggestive significance indicates that future studies with further increased sample size will be critical to identify additional disease‐associated loci in individuals of African ancestry. [ABSTRACT FROM AUTHOR]

A series of dioxidomolybdenum (VI) complexes, [MoO2(ESB)H2O]·DMF (1), [MoO2(ESB)MeOH] (2), and [MoO2(ESB)H2O]·EtOH (3), containing 3‐ethoxysalicylaldehyde benzoylhydrazone have been synthesized and analysed using various spectral and analytical techniques such as elemental analyses, IR spectra, UV–Vis absorption spectra, X‐ray crystallography, and Hirshfeld surface analysis. Based on the elemental and spectral analysis, six‐coordinate geometry was assigned for these complexes wherein the hydrazone ligand binds to the metal centre in its dianionic enolate form through ONO donor set. Distorted octahedral geometry of complexes 1 and 2 was evidenced from their crystal structures, which is typical for many cis‐dioxido complexes of MoVI. The proligand and the new complexes were examined for their DNA binding, DNA cleavage, and cytotoxic properties. The DNA binding efficiency of the compounds in terms of their binding constants (Kb) of the metal complexes was observed to be 1.3727 × 105 M−1, 3.0194 × 104 M−1, and 1.13206 × 104 M−1 for [MoO2(ESB)H2O]·DMF (1), [MoO2(ESB)MeOH] (2), and [MoO2(ESB)H2O]·EtOH (3), respectively, indicating that these complexes strongly bind to DNA. To determine the binding interactions of the complexes with DNA and protein (BSA), molecular docking studies were carried out. Gel electrophoresis study reveals the fact that the complexes cleaved supercoiled pUC‐18 DNA to nicked form (Form II) in the presence and absence of H2O2. The complexes showed significantly high cytotoxicity against MCF‐7 (breast cancer cells). [ABSTRACT FROM AUTHOR]

A straight‐forward approach for the synthesis of a dihydrofuro[2,3‐b]benzofuran derivatives has been achieved through a base‐mediated Michael addition of 1,3‐dicarbonyls to 2‐nitrobenzofurans followed by intramolecular cyclization. A variety of 1,3‐dicarbonyls, including cyclic as well as trifluoromethylated ones, have been subjected to react with 2‐nitrobenzofurans under optimal conditions, and the respective dihydrofuro[2,3‐b]benzofurans could be accessed in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

Absence seizures (AS), presenting as short losses of consciousness with staring spells, are a common manifestation of childhood epilepsy that is associated with behavioral, emotional, and social impairments. It has also been suggested that patients with AS are more likely to suffer from mood disorders such as depression and anxiety. This systematic review and meta‐analysis synthesizes human and animal models that investigated mood disorders and AS. Of the 1019 scientific publications identified, 35 articles met the inclusion criteria for this review. We found that patients with AS had greater odds of developing depression and anxiety when compared to controls (odds ratio = 4.93, 95% confidence interval = 2.91–8.35, p <.01). The included studies further suggest a strong correlation between AS and depression and anxiety in the form of a bidirectional relationship. The current literature emphasizes that these conditions likely share underlying mechanisms, such as genetic predisposition, neurophysiology, and anatomical pathways. Further research will clarify this relationship and ensure more effective treatment for AS and mood disorders. [ABSTRACT FROM AUTHOR]

Educational technology designs in developing countries mostly focus on making knowledge resources widely available, through MOOCs, repositories and computer‐based tutoring. The use of digital media for cognitive augmentation, particularly interactive designs that help learners understand modelling topics in STEM, is underexplored. We report a 3‐year design study examining this potential in the Indian context, testing two iterations of an interactive system, Touchy‐Feely Vectors (TFV). The design supports learning vectors, a modelling topic pre‐university students struggle with. Virtual lesson‐plans were co‐designed with teachers to augment — but not replace — their existing practices, and to address classroom and resource constraints. Pre‐post testing of TFV‐1 (a computer‐based prototype) showed that it helped students develop a more integrated vector concept, and improved their reasoning. Field‐implementation of TFV‐2 (a textbook‐linked touch‐screen based design) in 6‐classrooms (3‐Control, N=135; 3‐Experimental, N=131) showed that it fostered cognitive engagement in average‐students and geometry‐algebra integration (model‐based reasoning) in good‐students. These results, along with a requirements analysis based on textbooks, indicate that the interaction possibilities supported by different representational media critically shape student reasoning. The study also illustrates a systematic approach to design and test digital media systems that support cognitive augmentation in developing countries. Lay description: What is already known about this topic: Computational modelling is central to model‐based reasoning (MBR) in contemporary scientific practice. Education needs to change to support this new way of thinking. However, it is not clear how this could be done systematically in developing countries.Textbooks are thus not replaceable in developing nation contexts, and any digital media designed to help develop model‐based reasoning in students would need to work with textbooks and existing teaching/learning practice. It is unclear how this could be done.When learning basic model‐based reasoning using static textbook media, students struggle with core MBR topics like vectors. What this paper adds: The paper reports a 3‐year design‐based study, where a vector simulation system was developed (Touchy‐Feely Vectors), which addressed the following issues. Addressing 2 above, the study illustrates a design that builds on static textbook media and associated practices.Addressing 3 above, a 2‐phase field test of the design (N = 266) showed that the system changes student reasoning, towards better integration of algebra and geometry, while reasoning with vectors.Addressing 1 above, the study provides a new model to implement the learning of modelling using interactive simulations, in developing country classrooms.Addressing 1 above, the study offers a clear model for designing such interventions in developing country contexts.More broadly, the study reveals how the nature of the medium used to present science content changes student cognition and reasoning. Implications for practice and/or policy: For curricula: The design we present can be extended easily, to develop similar systems for other topics. The design also illustrates how teachers adopt technology when they participate in the design.For policy: This design provides a workable policy alternative to the costly model of the digital medium replacing current media and its teaching/learning practices.For Research and Pedagogy: Our results suggest that researchers and teachers need to examine the capabilities and constraints of different media while analysing learning difficulties, and develop ways to address these issues [ABSTRACT FROM AUTHOR]

Among all the bio‐metals, zinc and copper derivatives of ONS donor thiosemicarbazone have aroused great interest because of their potential biological applications. Multisubstituted thiosemicarbazone ligand H2dspt (3,5‐dichlorosalicylaldehyde‐N4‐phenylthiosemicarbazone) derived new ternary complexes like [Zn(dspt)(phen)]‧DMF (1) and [Cu(dspt)(phen)]‧DMF (2), and another thiosemicarbazone, H2dsct (3,5‐dichlorosalicylaldehyde‐N4‐cyclohexylthiosemicarbazone), derived [Cu(dsct)(bipy)]‧DMF (3). These complexes have been characterized by elemental analysis (CHNS), Fourier transform infrared (FT‐IR), ultraviolet–visible (UV–Vis) and proton nuclear magnetic resonance (1H‐NMR) spectra. The structures of the complexes were obtained by single‐crystal X‐ray diffraction analysis. Compounds 1 and 2 got crystallized in the monoclinic P21/c space group. The complexes showed interesting supramolecular interaction, which in turn stabilizes the complexes. The ground state electronic configurations of the complexes were studied using the B3LYP/LANL2DZ basis set, and ESP plots of complexes were investigated. The interaction of the complexes with calf thymus DNA (CT‐DNA) was studied using absorption and fluorescence spectroscopic methods. A UV study of the interaction of the complexes with calf thymus DNA (CT‐DNA) has shown that the complexes can effectively bind to CT‐DNA, and [Cu(dspt)(phen)]·DMF (2) exhibited the highest binding constant to CT‐DNA (Kb = 3.7 × 104). Fluorescence spectral studies also indicated that Complex 2 binds relatively stronger with CT DNA through intercalative mode, exhibiting higher binding constant (Kq = 4.7 × 105). The DNA cleavage result showed that the complexes are capable of cleaving the DNA without the help of any external agent. Molecular docking studies were carried out to understand the binding of complexes with the molecular target DNA. Complex 2 exhibited the highest cytotoxicity against human breast cancer cell line MD‐MBA‐231 (IC50 = 23.93 μg/mL) as compared to Complex 1 (IC50 = 44.40 μg/mL). [ABSTRACT FROM AUTHOR]

In the pharmaceutical industry, the goal of a supply planner is to make efficient capacity allocation decisions that ensure an uninterrupted supply of drug products to patients and to maintain product inventory levels close to the target stock. This task can be challenging due to the limited availability of manufacturing assets, uncertainties in product demand, fluctuations in production yields, and unplanned site downtimes. It is not uncommon to observe uneven distribution of product inventories with some products carrying excess inventories, while other products may be close to a stockout. Maintaining high stock levels can have economic repercussions due to the risk of expiration of unused products (whereas products facing a stockout can adversely affect the treatment regimen of patients). The network complexity of pharmaceutical supply‐chains coupled with regulatory constraints and siloed planning systems force supply planners to rely on manual (error‐prone) decision‐making processes. Such an approach results in suboptimal capacity allocation and inventory management decisions. In this work, we propose a stochastic optimization methodology for the production scheduling of multiple drug products in lyophilization units across multiple sites. The framework leverages information obtained from historical and forecast data to generate scenarios of uncertain parameters (e.g., yield, demand, and downtimes) that can realize in the future. The optimization model determines a product filling schedule that maintains product stock levels close to targets under diverse scenarios. We show that this approach helps in avoiding reactive scheduling and in maintaining a more robust production plan than deterministic procedures (which ignore uncertainty). Specifically, planning under a stochastic optimization approach reduces the number of scenarios under which backlogs are observed and also reduces the magnitude of the backlogs. [ABSTRACT FROM AUTHOR]

Purpose: An increasing number of implantable or external devices can impact whether patients can receive radiological imaging examinations. This study examines and tests the Neulasta (pegfilgrastim) Onpro on‐body injector in multiple imaging environments. Methods: The injector was analyzed for four imaging modalities with testing protocols and strategies developed for each modality. In x‐ray and computed tomography (CT), scans with much higher exposure than clinical protocols were performed with the device attached to an anthropomorphic phantom. The device was monitored until the completion of drug delivery. For magnetic resonance imaging (MRI), the device was assessed using a hand‐held magnet and underwent the magnetically induced displacement testing in a 1.5T clinical MRI scanner room. For ultrasound, magnetic field changes were measured around an ultrasound scanner system with three transducers. Results: For x‐ray and CT no sign of device error was identified during or after the high radiation exposure scans. Drug delivery was completed at expected timing with expected volume. For MRI the device showed significant attractive force towards the hand‐held magnet and a 50‐degree deflection angle at 50 cm from the opening of the scanner bore. No further assessment from the gradient or radiofrequency field was deemed necessary. For ultrasound the maximum magnetic field change from baseline was measured to be +11.7 μT in comparison to +74.2 μT at 4 inches from a working microwave. Conclusions: No device performance issue was identified under the extreme test conditions in x‐ray or CT. The device was found to be MR Unsafe. Magnetic field changes around an ultrasound system met the limitation set by manufacture. Patient ultrasound scanning is considered safe as long as the transducers do not inadvertently loosen the device. [ABSTRACT FROM AUTHOR]

This manuscript presents a robust strategy for selective Pb(II) sensing based on a fluorescence turn‐off mechanism using ZnS quantum dots (QDs) biosynthesized using Aspergillus sp. The biogenic nanoprobe displayed marked sensing efficiency in the presence of Pb ions over concentration ranges from 5 to 100 μM with limits of detection of around 2.45 μM. Performance optimization studies revealed that the maximum fluorescence quenching efficiency was obtained in the presence of [ZnS NPs] at 4 mg/ml, and alkaline pH of 10 recorded under stable ambient temperature for approximately 5 min for the quenching process. Advanced morphological analysis indicated that the bio‐sensing mechanism was essentially a surface‐based phenomenon in which the Pb ions were in very close proximity to the QDs and formed stable ground‐state Pb–ZnS complexes, resulting in a quenched fluorescence of the QDs. Simultaneously, a larger fraction of Pb ions interacted via collisions with the excited ZnS QDs and resulted in an effective energy transfer from the excited QDs to the Pb ions, therefore resulting in an obvious decrease in QD fluorescence. These insights were well supported by theoretical analysis using Stern–Volmer plots and sphere‐of‐action models. [ABSTRACT FROM AUTHOR]

The Western Ghats of peninsular India is a highly sensitive and threatened ecoregion of exceptional freshwater ichthyodiversity. The present study investigated the growth, mortality and stock characteristics of Hypselobarbus thomassi, an endemic cyprinid fish from the Parappar Reservoir of Western Ghats, on the basis of the length‐frequency data collected during the period from 2009 to 2011. The growth parameters of this species were estimated using the FiSAT program, and the asymptotic length (L∞) and growth constant (K) being 476.79 mm and 0.39 year−1, respectively. The age at zero length (t0) was calculated as −0.0485 year−1. The longevity (tmax) and growth performance index (ϕ) were reported as 7.69 years and 2.95. The estimated total mortality (Z), natural mortality (M) and fishing mortality (F) were 1.65, 0.38 and 1.27 year−1, respectively. The relative yield per recruit (Y/R) analysis revealed the exploitation rate (E) at different levels as E0.1 = 0.36, E0.5 = 0.28 and Emax = 0.42. The current exploration level (0.77) is higher than the optimum exploitation rate (Emax = 0.42), indicating an overexploitation of the H. thomassi population. Accordingly, needed management measures should include restrictions on fishing gear mesh sizes, reduced fishing effort and declaration of closed seasons and sanctuaries to protect this threatened species. [ABSTRACT FROM AUTHOR]

A 3‐year‐old boy presented with history of recurrent respiratory tract infections in infancy. Clinically he had hemodynamically significant pre‐tricuspid left‐to‐right shunt and no pulmonary hypertension. Transthoracic echocardiography delineated anomalous drainage of the left sided pulmonary veins to a dilated coronary sinus opening into the right atrium. Closer evaluation from the subxiphoid and right parasternal views led to the diagnosis of an associated type IIb coronary sinus septal defect. [ABSTRACT FROM AUTHOR]

In search of antioxidants with enriched potency, the present study focus on the design and synthesis of a dithiocarbohydrazone, H3TCL derived from thiocarbohydrazide and 3‐ethoxysalicylaldehyde and its coordination complexes with molybdenum, viz, [MoO2(HTCL)D] (1–2) (where D = methanol (1), DMSO (2)) and [MoO2(HTCL)D]·DMF (where D = H2O (3)). The synthesized compounds were characterised by elemental analysis, spectroscopic techniques (FT‐IR, UV–vis and 1H‐NMR), conductivity measurements and cyclic voltammetry. Moreover the solid state structures of all the three complexes were established by single crystal X‐ray diffraction analysis as mononuclear neutral species in which the molybdenum centre assumes a distorted octahedral geometry. The dithiocarbohydrazone binds to the molybdenum centre through its phenolate oxygen, O(1), azomethine nitrogen, N(1) and thioenolate sulfur, S(1) in a dianionic tridentate mode. The assessment of intermolecular contacts in the crystal arrangement was quantified using Hirshfeld surface analysis. Further the antioxidant potential of the dithiocarbohydrazone, H3TCL and its molybdenum complexes 1–3 were evaluated using 1,1‐diphenyl‐2‐picrylhydrazyl(DPPH), 2,2′‐azinobis‐3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) and total antioxidant assays. The antioxidant activities were then compared with standard antioxidant, L‐ascorbic acid. The antioxidant potential of the synthesized compounds were then validated by molecular docking studies. Molecular modelling study was achieved to evaluate the recognition of target compound at the binding pocket of the human antioxidant enzyme, 3MNG. The docking results showed that the complexes selectively bond to the vital amino acids present in the binding pocket of the target enzyme, 3MNG. [ABSTRACT FROM AUTHOR]

The bird cherry‐oat aphid (Rhopalosiphum padi L.) is a major pest of wheat (Triticum aestivum L.) and can cause up to 30% yield losses. Heritable plant resistance to aphids is both an economically and ecologically sound method for managing aphids. Here we report how the behaviour and performance of R. padi differs on two resistant, one susceptible wheat landrace and a susceptible elite wheat variety. Feeding behaviour differed among the genotypes, with aphids on resistant lines spending longer in the pathway phase and less time phloem feeding. These behaviours suggest that both inter‐ and intracellular factors encountered during pathway and phloem feeding phases could be linked to the observed aphid resistance. Locomotion and antennal positioning choice tests also revealed a clear preference for susceptible lines. Although feeding studies revealed differences in the first probe indicating that the resistance factors might also be located in the peripheral layers of the plant tissue, scanning electron microscopy revealed no difference in trichrome length and density on the surface of leaves. Aphids are phloem feeders and limiting the nutrient uptake by the aphids may negatively affect their growth and development as shown here in lower weight and survival of nymphs on resistant genotypes and decreased reproductive potential, with lowest mean numbers of nymphs produced by aphids on W064 (54.8) compared to Solstice (71.9). The results indicate that resistant lines markedly alter the behaviour, reproduction and development potential of R. padi and possess both antixenosis and antibiosis type of resistance. [ABSTRACT FROM AUTHOR]

Six new cis‐dioxidomolybdenum(VI) complexes featured with a tridentate ONO donor Schiff base derived from salicylidene‐2‐aminophenolato backbone have been synthesised and characterised by elemental analysis, spectroscopic techniques (like IR, UV‐vis and 1H‐NMR) and cyclic voltammetry. Suitable single crystals of the parent complex [MoO2L(MeOH)]2·H2O (1) was obtained by the slow evaporation of the mother liquor, whereas the crystals of the complexes 2‐6 were grown in coordinating solvents like ethanol, DMF, DMSO etc. and were characterised by single crystal X‐ray diffraction as monomers stabilised by the solvent molecules used for the recrystallization purpose. The structures of the complexes were further quantified using Hirshfeld surface analysis. The Schiff base acts as a colorimetric chemosensor for CN‐ ions in DMSO solution. The receptor‐CN‐ ion interaction and the sensing mechanism of the chemosensor were verified by colorimetric, UV‐vis, 1H‐NMR and FT‐IR spectroscopic studies. Hydroxyl moiety present in the receptor function as the binding site for cyanide ion thereby leading to its optical discrimination in presence of other anions by producing a visible colour change from colourless to yellow. Therefore the Schiff base sensor portrays estimable selectivity and sensitivity towards CN‐ ion. Additionally the Schiff base as well as the molybdenum complexes exhibit good third order non‐linear optical properties and optical power limiting when analysed by the Z‐scan technique. [ABSTRACT FROM AUTHOR]

Background: Early Onset Alzheimer Disease (EOAD, age at onset [AAO] < = 65) is a severe form of AD, often occurring when patients are still caring for children or adults. Despite this, most genetic studies of EOAD have focused on autosomal dominant forms, and there is little understanding of similarities and differences between early and late onset forms of AD (LOAD, [AAO]>65). To address this, we present a genome‐wide association study of non‐Mendelian EOAD and compare it to LOAD GWAS. Methods: Primary single‐variant analyses were performed using two additive logistic regression for case‐control models (full: SNPs, PCs, sex and APOE‐ɛ4 dosage as covariates; reduced: SNPs and PCs); secondary models included PCs+sex and PCs+APOE. Models were applied on data derived from the Alzheimer Disease Genetics Consortium (ADGC), composed by unrelated individuals. Samples varied from 1293‐1459 cases and 8894‐9366 controls for EOAD, and 8795‐9508 cases and 9702‐10273 controls for LOAD, depending on the considered model. The SNP heritability (h2) and genetic correlation (rg) were estimated using LD score regression. Gene‐based and pathway analysis (gene sets from Msigdb‐v7.0) were performed using FUMA/MAGMA‐v1.6. Results: We identified two novel loci associated with EOAD: Chromosome 4 (full model: chr4:102027610, P = 2.98×10−08, near PPP3CA gene) and Chromosome 12 (PCs+sex model: rs117001070, P = 2.11×10−08, intergenic between LINC02444 and LINC02882). We additionally confirmed BIN1 and APOE in the EOAD subset. Several known genes also showed a significant association with LOAD. Heritability analyses showed higher h2 values for EOAD (h2 = 0.29, 0.29, 0.29 and 0.27) than LOAD (h2 = 0.19, 0.16, 0.19, and 0.15), for full, reduced, PCs+sex and PCs+APOE models respectively. Genetic correlation showed moderate but incomplete genetic correlation between EOAD and LOAD. Other than APOE (p = 3.89×10−12), gene‐based tests showed nominal association for EOAD C8orf44‐SGK3 (p = 9.95×10−06), SGK3 (p = 2.01×10−05) and HIST1H2AC (p = 3.04×10−05), and plausible pathways such as HDL remodeling (p = 5.50×10−05) and positive regulation of cholesterol efflux (p = 9.79×10−05). These pathways were nominally associated with LOAD (p = 0.04 and p = 4.05×10−03). Conclusions: We identified two novel loci associated to EOAD not previously reported by LOAD studies. Heritability and genetic correlation results suggest that the genetic etiology of EOAD has an incomplete genetic overlap with LOAD. [ABSTRACT FROM AUTHOR]

Background: Early‐onset (≤65 years old) Alzheimer Disease (EOAD), which accounts for approximately 10% of all AD cases, is sometimes equated with dominantly inherited forms of AD (i.e., caused by known mutations in APP, PSEN1 or PSEN2). However, 90% of EOAD cases remain unexplained by these variants. This project aims to identify novel EOAD‐associated variants through a large‐scale, multi‐ethnic genome‐wide association (GWA) study. Method: We have leveraged the Alzheimer Disease Genetics Consortium (ADGC) GWAS dataset that is aligned to GRCh38 and imputed with the TOPMed imputation server. This includes 39 studies from non‐Hispanic Whites (NHW; CA = 3,202; CO = 5,782), 17 from African American (CA = 139; CO = 253), six from Asian (CA = 133; CO = 474), and seven from Hispanic (CA = 199; CO = 59) cohorts. Only the younger (≤65yo) and older participants (>80yo) were included for analysis as cases and controls, respectively. The genetic background was confirmed using PCA. We are performing single‐variant analysis to identify variants that confer a higher risk for EOAD. Result: Our preliminary single‐variant association analysis (using sex, PC1‐PC10 as covariates) emerging from the largest NHW cohort (CA = 3,202; CO = 5,782) have revealed nine different loci that were associated with EOAD at a suggestive P‐value<1×10−6. The strongest signal from our analysis was in the APOE region. Additionally, we identified three novel genome‐wide significant (P‐value <5×10−8) loci of interest at HLA‐DRB9 (rs9268852, P‐value = 2.9×10−9, OR = 1.22); FAM86B3P (rs73199790, P‐value = 3×10−11, OR = 1.32); and MSMB (rs2075895, P‐value = 2.83×10−16, OR = 1.26); while also confirming the previously identified loci at MS4A4A (rs7108663, P‐value = 1.13×10−10, OR = 0.80) and CR1 (rs6656401, P‐value = 2.54×10−12, OR = 1.32). We will perform qualitative associations on the other three ethnicities to confirm the transferability of these signals. Conclusion: Our single‐variant analysis has identified three novel loci associated with EOAD. This study is the largest genetic screening for risk and protective variants in EOAD and will be instrumental to identifying novel variants and pathways implicated in unexplained EOAD. Our future analysis includes gene‐based association and pathway analyses per ethnicity to identify variants that confer a higher risk for EOAD, followed by transethnic analysis to validate the comprehensive nature of these risk factors. Additionally, we have also generated GWAS data from the Knight‐ADRC participants, which will be merged with the ADGC datasets for our future analysis. [ABSTRACT FROM AUTHOR]

Background: In the largest Alzheimer disease (AD) genome‐wide association studies to date for African‐Americans (AA; Reitz et al. JAMA 2013; Kunkle at al. JAMA Neurol 2021) we previously identified in addition to APOE several novel susceptibility loci, including ABCA7, API5, RBFOX1 and IGF1R. We followed up these analyses with an increased sample size (2,913 cases, 5,802 controls) employing the African Genome Resource (AGR) panel. Method: Single‐variant association analysis was conducted adjusting for age, sex, principal components and subsequently APOE, applying logistic regression for case‐control and general estimating equations for family‐based datasets. Within‐study results were meta‐analyzed using METAL. Gene‐based and pathway analyses were conducted via MAGMA. Result: In addition to the previously reported AA risk loci, we identified three novel signals reaching genome‐wide significance at chromosomes 3p24 (TOP2B; P = 4.7×10−8), 3q26 (NCEH1; P = 3.7×10−8) and 9p23 (MPDZ; P = 1.7×10−8), and seventeen novel loci reaching suggestive significance at p ≤ 9×10−7. NCEH1 modulates cholesterol metabolism and is neuroprotective against α‐synuclein toxicity; MPDZ encodes a scaffolding protein involved in cytoskeleton remodeling. Top2B encodes a DNA topoisomerase involved in DNA transcription. Gene‐based analyses identified SLC39A3 (P = 2.9×10−6), involved in zinc transport, as a novel candidate gene. Pathway analyses support the notion that besides immunity, synaptic function, transcription/DNA repair, lipid processing, and intracellular trafficking, which overlap with the major AD‐associated pathways in non‐Hispanic Whites, also renal function is involved in AD etiology in African Americans. Conclusion: We identified several novel candidate loci for AD in AA. While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non‐Hispanic White individuals, the disease‐associated loci within these pathways differ. Identification of a significant number of loci at suggestive significance indicates that future studies with further increased sample size will be valuable to identify additional disease‐associated loci in this ethnic group. [ABSTRACT FROM AUTHOR]

Abstract: We present the development of a two‐component magnetic resonance (MR) fiducial system, that is, a fiducial marker device combined with an auto‐segmentation algorithm, designed to be paired with existing ultrasound probe tracking and image fusion technology to automatically fuse MR and ultrasound (US) images. The fiducial device consisted of four ~6.4 mL cylindrical wells filled with 1 g/L copper sulfate solution. The algorithm was designed to automatically segment the device in clinical abdominal MR images. The algorithm's detection rate and repeatability were investigated through a phantom study and in human volunteers. The detection rate was 100% in all phantom and human images. The center‐of‐mass of the fiducial device was robustly identified with maximum variations of 2.9 mm in position and 0.9° in angular orientation. In volunteer images, average differences between algorithm‐measured inter‐marker spacings and actual separation distances were 0.53 ± 0.36 mm. “Proof‐of‐concept” automatic MR‐US fusions were conducted with sets of images from both a phantom and volunteer using a commercial prototype system, which was built based on the above findings. Image fusion accuracy was measured to be within 5 mm for breath‐hold scanning. These results demonstrate the capability of this approach to automatically fuse US and MR images acquired across a wide range of clinical abdominal pulse sequences. [ABSTRACT FROM AUTHOR]

Abstract: An implantable anticancer device (IAD) amenable to eradicate local regional recurrence (LRR) of breast cancer as well as to enhance the breast reconstruction during/after therapy is proposed for the first time. The IAD is fabricated by incorporating the superparamagnetic graphene oxide doxorubicin nanocomposite of size ≈200 nm in a nanofiber matrix to enable the sustained and tumor specific anticancer drug release over 60 d in vitro with a minimum initial burst release and the repeated hyperthermic capability in an alternating magnetic field to ensure the synergistic inhibition of LRR. The IAD also enriches the reconstruction of poor breast cosmesis that resulted from the surgical treatment by supporting the lipofilling of the surgical residual cavity to induce the adipogenic process. Moreover, the noninvasive monitoring capability of IAD through magnetic resonance imaging augments to the effective patient care. Thus, this work reports a new and reliable concept by introducing the multifunctional IAD possessing enhanced specificity with a real‐time monitoring capability and long‐term anticancer efficacy as a potential platform for synergistic inhibition of LRR and a great promise for the in situ breast reconstruction ability for better breast cosmesis. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we report the formation of two quasi‐isostructural polymorphs (α and β) of a Ni(II) salphen‐type Schiff base complex using solvent evaporation technique. The polymorphs are inclusion compounds with guest water molecules exhibiting similar spectroscopic and thermal characteristics. Single crystal XRD (X‐ray Diffraction) analyses reveal the subtle differences in packing and supramolecular interactions which are quantified using Hirshfeld and 2D finger print analyses. Electrostatic potential analysis shows significant difference in potential distribution in the two molecules. The compositional analysis of the frontier orbitals and differences among the atomic charge distribution of the polymorphs are established using DFT (Density Functional Theory) calculations. Apart from highlighting the strength of encapsulation, DFT study substantiates the formation of inclusion compounds through single point energy calculations. Effects of inherent differences in the polymorphs on potential biological activity are probed using in silico molecular docking with B‐DNA and Human Serum Albumin (HSA). The α form shows superior bioactivity while β form excels in water encapsulation. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association between renal tumour complexity and outcomes in a large cohort of patients undergoing percutaneous cryoablation ( PCA). Patients and Methods Patients with renal tumours treated with PCA were identified using our prospectively maintained ablation registry (2003-2015). Salvage procedures and inherited tumour syndromes were excluded. The associations between R.E.N.A.L. nephrometry score ( NS) and risk of complications, renal function impairment, local failure and cancer-specific mortality ( CSM) were evaluated using univariate and multivariable logistic, linear and Cox regression models. Results The cohort included 618 tumours treated during 580 procedures in 565 patients. The median (interquartile range [ IQR]) follow-up was 34 (14.66) months. Complications (any grade) during a procedure ( n[total] = 87, 15%) were more frequent with higher NS ( NS 4-6: 10%; NS 7-9: 14%; NS 10-12: 36%; P < 0.001). Higher NS was independently associated with risk of complications (odds ratio [ OR; per 1 point] = 1.3; 95% confidence interval [ CI] 1.2-1.5; P < 0.001). Of all the NS components, tumour size was the most strongly associated with complication risk ( OR 3.4; 95% CI 2.2-5.2; P < 0.001). The median ( IQR) decline in glomerular filtration rate ( GFR) from baseline was 9% (0, 22) at last follow-up. Each additional point in NS was associated with a 1.3% (95% CI 0.4-2.1; P = 0.005) greater GFR decline from baseline. NS was not significantly associated with local failure ( n [total] = 14, 2%; NS 4-6: 2%; NS 7-9: 3%; NS 10-12: 5%; P = 0.32) or CSM ( n [total] = 8, 2%; NS 4-6: 2%; NS 7-9: 3%; NS 10-12: 2%; P = 0.88). Conclusion In high-complexity tumours PCA was associated with a tumour size-driven increased risk of post-procedural complications. Higher NS was associated with a small, clinically minor additional decline in renal function. Risks for local failure and CSM were low, regardless of tumour complexity. [ABSTRACT FROM AUTHOR]

ABSTRACT In this paper, an approach to analyze the bone mineral density (BMD) based on microwave reflectivity is presented The proposed method enables us to overcome the health risks associated with diagnostic techniques such as X-rays for repeated study of the rate of mineralization in the case of fractures or de-mineralization in the case of osteoporosis. The proposed method is used to demonstrate the application of microwaves for continuous observation of skull healing process during post-cranial surgery period. The proposed technique can be a potential clinical model in future for extracting target characteristics such as bone deposition thickness and other cranial defects. Based on the conclusions of wideband measured data and signal processing techniques, we propose to design the Transceiver using ultra-wideband (UWB) pulsed technology. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 59:21-26, 2017 [ABSTRACT FROM AUTHOR]

Coordination of endomembrane biogenesis with cell cycle progression is considered to be important in maintaining cell function during growth and development. We previously showed that the disruption of PHOSPHATIDIC ACID PHOSPHOHYDROLASE ( PAH) activity in Arabidopsis thaliana stimulates biosynthesis of the major phospholipid phosphatidylcholine ( PC) and causes expansion of the endoplasmic reticulum. Here we show that PC biosynthesis is repressed by disruption of the core cell cycle regulator CYCLIN- DEPENDENT KINASE A;1 ( CDKA;1) and that this repression is reliant on PAH. Furthermore, we show that cyclin-dependent kinases ( CDKs) phosphorylate PAH1 at serine 162, which reduces both its activity and membrane association. Expression of a CDK-insensitive version of PAH1 with a serine 162 to alanine substitution represses PC biosynthesis and also reduces the rate of cell division in early leaf development. Together our findings reveal a physiologically important mechanism that couples the rate of phospholipid biosynthesis and endomembrane biogenesis to cell cycle progression in Arabidopsis. [ABSTRACT FROM AUTHOR]

CeO2/CoPc nanocomposites were synthesized by simple chemical method. Thermal behavior of these nanocomposites was studied by thermogravimetric and differential thermal analysis. The as-synthesized nanocomposite samples were characterized by various techniques. A decrease in band-gap energy together with an improved absorption intensity of the composite material confirms the role of the cobalt phthalocyanine in the absorption properties of CeO2/CoPc composite. This study confirms structural modifications and extended spectral response of the synthesized CeO2/CoPc nanocomposites. The results demonstrate that CeO2/CoPc nanocomposite samples are promising materials for organic light-emitting diodes, solar cells, and optoelectronic devices. [ABSTRACT FROM AUTHOR]

Density Functional Theory (DFT)-based Global reactivity descriptor calculations have emerged as powerful tools for studying the reactivity, selectivity, and stability of chemical and biological systems. A Python-based module, PyGlobal has been developed for systematically parsing a typical Gaussian outfile and extracting the relevant energies of the HOMO and LUMO. Corresponding global reactivity descriptors are further calculated and the data is saved into a spreadsheet compatible with applications like Microsoft Excel and LibreOffice. The efficiency of the module has been accounted by measuring the time interval for randomly selected Gaussian outfiles for 1000 molecules. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor ( BDNF) regulates synaptic strengthening and memory consolidation, and altered BDNF expression is implicated in a number of neuropsychiatric and neurodegenerative disorders. BDNF potentiates N-methyl-D-aspartate receptor function through activation of Fyn and ERK1/2. STriatal-Enriched protein tyrosine Phosphatase ( STEP) is also implicated in many of the same disorders as BDNF but, in contrast to BDNF, STEP opposes the development of synaptic strengthening. STEP-mediated dephosphorylation of the NMDA receptor subunit GluN2B promotes internalization of GluN2B-containing NMDA receptors, while dephosphorylation of the kinases Fyn, Pyk2, and ERK1/2 leads to their inactivation. Thus, STEP and BDNF have opposing functions. In this study, we demonstrate that manipulation of BDNF expression has a reciprocal effect on STEP61 levels. Reduced BDNF signaling leads to elevation of STEP61 both in BDNF+/− mice and after acute BDNF knockdown in cortical cultures. Moreover, a newly identified STEP inhibitor reverses the biochemical and motor abnormalities in BDNF+/− mice. In contrast, increased BDNF signaling upon treatment with a tropomyosin receptor kinase B agonist results in degradation of STEP61 and a subsequent increase in the tyrosine phosphorylation of STEP substrates in cultured neurons and in mouse frontal cortex. These findings indicate that BDNF-tropomyosin receptor kinase B signaling leads to degradation of STEP61, while decreased BDNF expression results in increased STEP61 activity. A better understanding of the opposing interaction between STEP and BDNF in normal cognitive functions and in neuropsychiatric disorders will hopefully lead to better therapeutic strategies. [ABSTRACT FROM AUTHOR]

The human hypothalmus produces an endogenous membrane Na[sup +] -K[sup +] ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na[sup +] -K[sup +] ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na[sup +] -K[sup +] ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg[sup ++] . The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na[sup +] -K[sup +] ATPase inhibition. The role of membrane Na[sup +] -K[sup +] ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na[sup +] -K[sup +] ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. Copyright © 2002 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Genomic studies of Alzheimer disease (AD) have primarily focused on non‐Hispanic White (NHW) participants affected by the late‐onset form (LOAD; onset age: >65), or the study of early onset AD (EOAD; onset age <=65) cases showing Mendelian inheritance patterns associated with mutations in the APP, PSEN1 and PSEN2 genes. However, mutations in these three genes explain ∼10% of EOAD cases. There are no large‐scale efforts to collect and study EOAD cases not explained by these genes, despite this unexplained category accounting for ∼90% of EOAD cases. Method: To address this, we aim to identify additional EOAD‐associated variants, genes and pathways through a large‐scale whole‐genome sequencing (WGS) study of unexplained EOAD. We will include cases from several AD cohorts, including the Resource for Early‐onset Alzheimer Disease Research (READR), the Knight‐ADRC at Washington University, the Alzheimer's Disease Genetics Consortium (ADGC), and others. Generating and harmonizing a dataset of 200 non‐Hispanic White (NHW) and Caribbean Hispanic (CH) multiplex EOAD families, over 5,400 EOAD singletons and over 13,000 unrelated, cognitive controls, all with WGS, this project will yield the largest EOAD genomics dataset to‐date, improving statistical power for variant identification and allowing us to assess the impact of specific factors such as APOE genotype, vascular risk factors, and neuropsychiatric comorbidities. The inclusion of a large set of Hispanic families and singletons allows the examination of EOAD risk in a significantly understudied population. Analyses will comprise both linkage and association‐based approaches, analyses of polygenic and ancestry effects, and a thorough examination of neurocognitive, neuropsychiatric and cardiovascular endophenotypes. Result: When completed this study will point to novel genetic contributors to EOAD, shed light on the mechanisms of AD and facilitate the development of novel prediction models and therapeutics. Conclusion: Sampling, phenotyping and sequencing analysis protocols will be complementary to and compatible with the existing LOAD genomics resources, such as the Alzheimer Disease Sequencing Project (ADSP) and related studies. This phenotypic and genomic consistency, together with the use of existing AD infrastructure (NIAGADS), allows for immediate integration with the leading efforts on LOAD, enabling rapid large‐scale investigation of a variety of additional critical AD genomics hypotheses. [ABSTRACT FROM AUTHOR]

Background: Alzheimer disease (AD) is a degenerative brain disease, being the most common cause of progressive dementia and listed as the sixth leading cause of mortality in the USA. It is often described as either early onset (EOAD, age at onset, [AAO] <= 65) or late onset (LOAD, [AAO]>65). Non‐Mendelian EOAD (not monogenic; nmEOAD) has irregular inheritance patterns and fluctuating AAO, characteristics also present in LOAD cases. There is still a lack of evidence in the literature depicting the similarities (if any) between nmEOAD and LOAD forms, being unclear how much genetic etiology is shared by the two forms of AD. To shed light to this question, a genome‐wide association study (GWAS) and heritability analyses of nmEOAD and LOAD were performed. Method: Genetic data on 21,622 individuals from the Alzheimer Disease Genetics Consortium (ADGC) were used: (1,476 nmEOAD, 9,695 LOAD and 10,451 control). Single‐variant association analyses were performed using logistic regression under two models: (1) ancestry plus SNP, and (2) ancestry, sex, APOE dosage, and SNP. nmEOAD and LOAD were considered separately. LD score regression was used to estimate the SNP heritability (h2) and genetic correlation (rg), considering two additional models: (3) ancestry, sex, and SNP and (4) ancestry, APOE dosage and SNP. Result: Several known candidate genes confirmed for LOAD along with novel regions associated with immune and cell‐signaling pathways in nmEOAD models. Gene based tests showed significant association for APOE gene (Chr19): nmEOAD (p=3.89x10‐16 and p=4.29x10‐12) and LOAD (p=1.07x10‐65 and p=1.12x10‐14), models (1) and (2) respectively. Heritability analyses showed higher h2 values for EOAD (h2=0.24, 0.23, 0.25 and 0.24) than LOAD (h2=0.18, 0.14, 0.18, and 0.14) for models (1) to (4) respectively. Genetic correlation showed moderate genetic overlap between EOAD and LOAD only for models: (2) rg=0.35 (p=0.0283) and (4) rg=0.34 (p=0.0261). Conclusion: GWAS and heritability analysis suggest that the genetic etiology of EOAD has a noncomplete genetic overlap with LOAD, with a moderate overlap when APOE dosage is modeled and a minimal overlap otherwise (APOE effect). The results also suggest a stronger polygenic effect in EOAD than LOAD, confirming the need for additional genomics efforts in nmEOAD. [ABSTRACT FROM AUTHOR]